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Phosphorylated insulin like growth factor

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https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#1
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28794431/macrophage-jak2-deficiency-protects-against-high-fat-diet-induced-inflammation
#2
Harsh R Desai, Tharini Sivasubramaniyam, Xavier S Revelo, Stephanie A Schroer, Cynthia T Luk, Prashanth R Rikkala, Adam H Metherel, David W Dodington, Yoo Jin Park, Min Jeong Kim, Joshua A Rapps, Rickvinder Besla, Clinton S Robbins, Kay-Uwe Wagner, Richard P Bazinet, Daniel A Winer, Minna Woo
During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2(-/-)) mice gained less body weight compared to wildtype littermate control (M-JAK2(+/+)) mice and were protected from HFD-induced systemic insulin resistance...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793874/picropodophyllin-ppp-is-a-potent-rhabdomyosarcoma-growth-inhibitor-both-in-vitro-and-in-vivo
#3
Maciej Tarnowski, Marta Tkacz, Katarzyna Zgutka, Joanna Bujak, Patrycja Kopytko, Andrzej Pawlik
BACKGROUND: Insulin-like growth factors and insulin are important factors promoting cancer growth and metastasis. The molecules act through IGF1 (IGF1R) and insulin (InsR) receptors. Rhambodmyosarcomas (RMS) overproduce IGF2 - a potent ligand for IGF1R and, at the same time, highly express IGF1 receptor. The purpose of the study was to evaluate possible application of picropodophyllin (PPP) - a potent IGF1R inhibitor. METHODS: In our study we used a number of in vitro assays showing influence of IGF1R blockage on RMS cell lines (both ARMS and ERMS) proliferation, migration, adhesion, cell cycling and signal transduction pathways...
August 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28753127/igf2-mrna-binding-protein-2-is-a-tumor-promoter-that-drives-cancer-proliferation-through-its-client-mrnas-igf2-and-hmga1
#4
Ning Dai, Fei Ji, Jason Wright, Liliana Minichiello, Ruslan I Sadreyev, Joseph Avruch
The gene encoding the Insulin-like Growth Factor 2 mRNA binding protein 2/IMP2 is amplified and overexpressed in many human cancers, accompanied by a poorer prognosis. Mice lacking IMP2 exhibit a longer lifespan and a reduced tumor burden at old age. Herein we show in a diverse array of human cancer cells that IMP2 overexpression stimulates and IMP2 elimination diminishes proliferation by 50-80%. In addition to its known ability to promote the abundance of Insulin-like Growth Factor 2/IGF2, we find that IMP2 strongly promotes IGF action, by binding and stabilizing the mRNA encoding the DNA binding protein HMGA1, a known oncogene...
July 28, 2017: ELife
https://www.readbyqxmd.com/read/28744224/downregulated-translation-initiation-signaling-predisposes-low-birth-weight-neonatal-pigs-to-slower-rates-of-muscle-protein-synthesis
#5
Ying Chen, Sydney R McCauley, Sally E Johnson, Robert P Rhoads, Samer W El-Kadi
Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#6
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#7
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708244/mir-199a-3p-is-involved-in-estrogen-mediated-autophagy-through-the-igf-1-mtor-pathway-in-osteocyte-like-mlo-y4-cells
#8
Jiayao Fu, Lingyu Hao, Yawen Tian, Yang Liu, Yijing Gu, Junhua Wu
To date, evidence indicates that estrogen partially modulates cellular processes through microRNAs. Autophagy is a catabolic process that is regulated by multiple factors and is associated with skeletal diseases. However, whether estrogen regulates osteocyte autophagy via microRNAs is largely unknown. In this study, we observed the up-regulation of microRNA-199a-3p, a post-transcriptional regulatory factor, in osteocytic areas in ovariectomized (OVX) mice. The mature forms of miR-199a-3p and pri-miR-199a were produced in response to estrogen signaling in osteocyte-like MLO-Y4 cells...
July 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28706506/identification-of-brca1-as-a-potential-biomarker-for-insulin-like-growth-factor-1-receptor-targeted-therapy-in-breast-cancer
#9
Tali Cohen-Sinai, Zoya Cohen, Haim Werner, Raanan Berger
The insulin-like growth factor-1 receptor (IGF1R) emerged in recent years as a promising therapeutic target in oncology. Identification of potential biomarkers capable of predicting response to IGF1R-targeted therapy is of cardinal importance. Tumor suppressor BRCA1 has important roles in multiple pathways, including gene transcription, DNA damage repair, and control of apoptosis. Early studies have identified the IGF1R gene as a downstream target for inhibitory regulation by wild-type, but not mutant, BRCA1...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28694839/gene-expression-profiling-of-whole-blood-cells-supports-a-more-efficient-mitochondrial-respiration-in-hypoxia-challenged-gilthead-sea-bream-sparus-aurata
#10
Juan Antonio Martos-Sitcha, Azucena Bermejo-Nogales, Josep Alvar Calduch-Giner, Jaume Pérez-Sánchez
BACKGROUND: Acclimation to abiotic challenges, including decreases in O2 availability, requires physiological and anatomical phenotyping to accommodate the organism to the environmental conditions. The retention of a nucleus and functional mitochondria in mature fish red blood cells makes blood a promising tissue to analyse the transcriptome and metabolic responses of hypoxia-challenged fish in an integrative and non-invasive manner. METHODS: Juvenile gilthead sea bream (Sparus aurata) were reared at 20-21 °C under normoxic conditions (> 85% O2 saturation) followed by exposure to a gradual decrease in water O2 concentration to 3...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28694663/inhibition-of-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-by-liuwei-dihuang-pill-in-db-db-mice
#11
Shan Zhuang, Yong-Mei Jian, Yong-Ning Sun
AIM: To investigate the inhibitory effect of Liuwei Dihuang Pill (LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea (MNU) in diabetic mice. METHODS: Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28693193/allicin-inhibits-the-invasion-of-lung-adenocarcinoma-cells-by-altering-tissue-inhibitor-of-metalloproteinase-matrix-metalloproteinase-balance-via-reducing-the-activity-of-phosphoinositide-3-kinase-akt-signaling
#12
Ling Huang, Yuanhong Song, Jianping Lian, Zhiwei Wang
Allicin, the main active principle associated with Allium sativum chemistry, has various antitumor activities. However, to the best of our knowledge, there is no available information to address the anti-invasive effect and associated mechanism in lung adenocarcinoma. In the present study, cell viability assay, cell adhesion assay, western blot analysis, Transwell migration and invasion assays and reverse transcription-quantitative polymerase chain reaction were performed. Allicin was identified to inhibit the adhesion, invasion and migration of lung adenocarcinoma cells in a dose-dependent manner, accompanied by decreasing mRNA and protein levels of matrix metalloproteinase (MMP)-2 and MMP-9...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28686668/molecular-interactions-of-epha4-growth-hormone-receptor-janus-kinase-2-and-signal-transducer-and-activator-of-transcription-5b
#13
Takahiro Sawada, Daiki Arai, Xuefeng Jing, Masayasu Miyajima, Stuart J Frank, Kazushige Sakaguchi
We previously reported that EphA4, a member of the Eph family of receptor tyrosine kinases, is an important modulator of growth hormone (GH) signaling, leading to augmented synthesis of insulin-like growth factor 1 (IGF1) for postnatal body growth. In the present study, we report the molecular interactions of EphA4, GH receptor (GHR), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 5B (STAT5B). EphA4 binds to GHR at both its extracellular and intracellular domains and phosphorylates GHR when stimulated with a ligand...
2017: PloS One
https://www.readbyqxmd.com/read/28685895/restoration-of-microrna-708-sensitizes-ovarian-cancer-cells-to-cisplatin-via-igf2bp1-akt-pathway
#14
Xuying Qin, Linlin Sun, Jing Wang
A previous study has shown that microRNA-708 (miR-708) functions as a metastasis suppressor in ovarian cancer. In this study, we aimed to explore its implication in regulating cisplatin sensitivity in ovarian cancer cells. To this end, ovarian cancer cells were transfected with miR-708-expressing plasmids or vector before treatment with different concentrations of cisplatin for 48 h. The 50% inhibitory concentration (IC50) value was calculated. Apoptosis was analyzed by measuring caspase-3 activity. The target gene mediating the function of miR-708 was identified...
July 7, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#15
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28682648/kinase-inhibitors-of-the-igf-1r-as-a-potential-therapeutic-agent-for-rheumatoid-arthritis
#16
Hiroshi Tsushima, Shinji Morimoto, Maki Fujishiro, Yuko Yoshida, Kunihiro Hayakawa, Takuya Hirai, Tomoko Miyashita, Keigo Ikeda, Ken Yamaji, Kenji Takamori, Yoshinari Takasaki, Iwao Sekigawa, Naoto Tamura
We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro...
July 6, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28677801/modulation-of-igf2bp1-by-long-non-coding-rna-hcg11-suppresses-apoptosis-of-hepatocellular-carcinoma-cells-via-mapk-signaling-transduction
#17
Yantian Xu, Yuanwen Zheng, Hongyan Liu, Tao Li
Hepatocellular carcinoma (HCC) is a common malignancy of the liver. HCG11 is a member of long non‑coding family, upregulation of which in HCC was proved by our previous study. In the present study, the role of HCG11 in the development of HCC was detected by focusing on the interaction between HCG11 and its target protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1). The expression status of HCG11 and IGF2BP1 was first investigated with clinical HCC samples. Then the expressions of HCG11 and IGF2BP1 were both inhibited in the human HCC cell line HepG2 and the cell viability, proliferation, apoptosis and metastasis potential of HepG2 cells were assessed...
July 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28674230/cdna-cloning-structural-analysis-snp-detection-and-tissue-expression-profile-of-the-igf1-gene-in-malabari-and-attappady-black-goats-of-india
#18
Thomas Naicy, Thirupathy Venkatachalapathy, Thazhathuveettil Aravindakshan, Kunniyoor Cheemani Raghavan, Mangattumuruppel Mini, Kulangara Shyama
Insulin-like growth factor 1 (IGF1) plays an important role in growth, reproduction, foetal development and cell proliferation. The present study was conducted to clone and sequence the full-length coding sequence of the caprine IGF1 gene from Attappady Black and Malabari breeds, two indigenous goat breeds of south India, to analyse its structure, and to ascertain the relative abundance of IGF1 mRNA in different tissues. The caprine IGF1 cDNA (GenBank accession nos: KJ549851 and KJ549852) contained a 465-bp open reading frame encoding IGF1 protein with 154 amino acid residues...
June 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28656297/klotho-suppresses-tumor-progression-via-inhibiting-igf-1r-signaling-in-t%C3%A2-cell-lymphoma
#19
Xiangxiang Zhou, Ya Zhang, Ying Li, Yangyang Xu, Lingyan Zhang, Ying Li, Xin Wang
Klotho is a transmembrane protein and acts as an upstream modulator of insulin-like growth factor-1 receptor (IGF-1R) signaling, which was indicated to be involved in the pathogenesis of solid cancer and hematological malignancies, including T‑cell lymphoma. Although Klotho was recently identified as a tumor suppressor in several types of human malignancies, the potential role of Klotho in T‑cell lymphoma has not been reported. In the present study, we investigated the expression level and the molecular events of Klotho in T‑cell lymphoma...
June 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28656233/resveratrol-inhibits-hypoxia-induced-proliferation-and-migration-of-pulmonary-artery-vascular-smooth-muscle-cells-by-inhibiting-the-phosphoinositide-3-kinase-protein-kinase-b-signaling-pathway
#20
Zhanjiang Guan, Li Shen, Huan Liang, Haitao Yu, Bingchang Hei, Xianguo Meng, Lei Yang
Hypoxia is a risk factor for severe chronic obstructive pulmonary disease, which aggravates the disease and may cause mortality by inducing hypoxic pulmonary hypertension (HPH). Proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) may mediate this effect. Resveratrol is a phenolic compound extracted from a plant and has been reported to alleviate HPH, although the underlying mechanisms remained to be elucidated. In cancer, resveratrol has been reported to abrogate the phosphoinositide 3‑kinase/protein kinase B (AKT) signaling pathway, thereby inhibiting tumor development...
August 2017: Molecular Medicine Reports
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